ENZYME INHIBITION BY DERIVATIVES OF PHENOTHIAZINE: III. CATALASE, CYTOCHROME OXIDASE, AND DEHYDROGENASES

1942 ◽  
Vol 20b (12) ◽  
pp. 284-290 ◽  
Author(s):  
H. Bruce Collier ◽  
Della E. Allen
Keyword(s):  
Cytochrome Oxidase ◽  
Succinic Dehydrogenase ◽  
Lactic Dehydrogenase ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Leuco Form ◽  
Dehydrogenase System ◽  
Living Organisms ◽  
Relationship Of ◽  
Derivatives Of

The inhibition of liver catalase and of cytochrome oxidase by leucophenothiazone has been confirmed by manometric methods. Phenothiazine sulphoxide is a powerful catalase inhibitor, its activity being much greater at pH 5.3 than at neutrality.The succinoxidase activity of beef heart is inhibited by phenothiazone and by thionol. Phenothiazone in its oxidized form acts upon the succinic dehydrogenase, while the leuco form inhibits the cytochrome oxidase.Phenothiazone is reduced by the yeast lactic dehydrogenase system, and the enzyme activity is markedly decreased. Urease is also partially inhibited, whereas the effect of phenothiazone upon d-amino-acid oxidase is almost negligible.The possible relationship of these findings to the action of phenothiazine upon living organisms is discussed.

Synthesis and Screening of Substances acting by Alkylation and Metabolic Inhibition

1967 ◽  
Vol 17 (1) ◽  
pp. 67-77 ◽  
Author(s):  
A. De Barbieri
Keyword(s):  
Alkylating Agents ◽  
White Cell Count ◽  
Succinic Dehydrogenase ◽  
Normal Liver ◽  
Lactic Dehydrogenase ◽  
Liver Mitochondria ◽  
Spleen Weight ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Enzyme Systems

SummaryMolecular carriers with alkylating sites and sites endowed with antimetabolic activity were synthesized.Phenylalanine and hydroxyphenylalanine having a dichlorodiethylamino group in the benzene ring were chosen as alkylating agents because of their capability to form peptides with natural and antagonist aminoacids.The chemotherapeutic screening was carried out according to CCNSG rules with the only variant that the determination of the weight of the tumors of the treated mice was carried out on the day subsequent to that indicated by the CCNSC, i.e. at the 9th day after tumor implantation. In this same day the spleen weight was determined also. On the previous day, the white cell count was carried out and in way it was allowed an evaluation of the hemotoxicity.The optical isomerism of the compounds plays a fundamental rôle in the chemotherapeutic activity.Examples of different isomers of the tripeptide phenylalanyl-ethionyl-m-sarco-lysine and of the tetrapeptide arginyl-p-fluorophenyl-alanyl-glycyl-m-sarcolysine, endowed with markedly different chemotherapeutic activities (from o to 90) in relation to the different stereochemical configuration are reported.Oxidative phosphorylation, ATPase, glycolysis, Nadase, succinic dehydrogenase, cytochrome-oxidase, glutamic dehydrogenase, lactic dehydrogenase amino acid oxidase, proteolysis were studied in biochemical pharmacology investigations.The active compounds bring the phosphorylation ratio to zero in Sarcoma 180 mitochondria at doses reducing the P/O by 40-50% in normal liver mitochondria.Interesting observations are pointed out for other enzyme systems, showing the specificity of the activity of some peptides at the biochemical level on tumor enzyme systems in comparison with the same enzyme systems of normal tissues.

scholarly journals THE METABOLISM OF THE KIDNEY IN EXPERIMENTAL RENAL HYPERTENSION

1945 ◽  
Vol 82 (4) ◽  
pp. 227-240 ◽  
Author(s):  
Sigwin B. Raska
Keyword(s):  
Cytochrome C ◽  
Cytochrome Oxidase ◽  
Amine Oxidase ◽  
Renal Hypertension ◽  
Succinic Dehydrogenase ◽  
Inhibitory Effect ◽  
Acid Oxidase ◽  
Tissue Slices ◽  
Amino Acid Oxidase ◽  
Experimental Renal Hypertension

These investigations are part of an attempt to study and interpret the intermediary metabolism of the kidneys in experimental renal hypertension. Hypertension was produced in dogs by the clamping procedure of Goldblatt and associates or by the silk perinephritis method of Page. Enzymatic studies were made by means of Warburg's manometric method. Cytochrome c was in addition determined spectrophotometrically. Tissue slices, homogenized tissue, and tissue extracts were used. A study of the cytochrome c concentration and the activities of the cytochrome oxidase and succinic dehydrogenase systems of kidneys from normal dogs and dogs with experimental renal hypertension was made. It was found that the cytochrome c concentration and the activities of the cytochrome oxidase and succinic dehydrogenase systems were markedly lower in the kidney slices and in the tissue suspensions from hypertensive dogs. Tissue suspensions and extracts of kidneys from hypertensive dogs showed an inhibitory effect on the activity of the cytochrome oxidase and succinic dehydrogenase, and the amine oxidase systems. Renin preparations also showed a marked inhibitory effect on the activities of cytochrome oxidase, succinic dehydrogenase, l-amino acid oxidase, and amine oxidase systems. A significant increase was found in the kidney of dogs whose other kidney had been removed or subjected to Goldblatt's or Page's technique in the activities of the cytochrome-cytochrome oxidase system, the succinic dehydrogenase system, and in the concentration of nucleotide-bound phosphorus, of flavin-adenine dinucleotide, and of the nicotinamide-adenine dinucleotides (coenzymes I and II). From the results of these studies it can be concluded that an increase in the concentration and activity of the respiratory enzymes precedes hypertrophy of the kidney. This can be explained by the assumption that an increase in the activity of the respiratory biocatalysts acts as a stimulus for cell growth and multiplication.

scholarly journals The ultrastructural cytochemistry of lactic dehydrogenase, succinic dehydrogenase, dihydro-nicotinamide adenine dinucleotide diaphorase and cytochrome oxidase activities in hair cell mitochondria of the guinea pig cochlea.

1975 ◽  
Vol 23 (3) ◽  
pp. 216-234 ◽  
Author(s):  
G J Spector
Keyword(s):  
Hair Cell ◽  
Cytochrome Oxidase ◽  
Nicotinamide Adenine Dinucleotide ◽  
Succinic Dehydrogenase ◽  
Lactic Dehydrogenase ◽  
Nicotinamide Adenine ◽  
Fixation Method ◽  
Inner Mitochondrial Membrane ◽  
Tetrazolium Chloride ◽  
Outer Compartment

The use of cinnamyl nitroblue tetrazolium chloride (DS-NBT) in dehydrogenase experiments (lactic dehydrogenase, succinic dehydrogenase, nicotinamide adenine dinucleotide diaphorase) and 3,3'-diaminobenzidine tetrahydrochloride (DAB) in cytochrome oxidase experiments indicated that mitochondrial oxidoreduction reactions from nicotinamide adenine dinucleotide to cytochrome oxidase are located on the inner mitochondrial membrane in the outer compartment and the intracristate spaces. These reactions behave according to the chemiosmotic hypothesis. The cochlear hair cell mitochondria are cytochemically indistinguishable from free liver mitochondria. The heterogeneous mitochondrial staining pattern is related to the osmolarity of the incubation media, solubility of the enzymes and pH of the medium, but not to the fixation method.

MOLECULAR BIOLOGICAL STUDIES ON STRUCTURE-FUNCTION RELATIONSHIP OF D-AMINO ACID OXIDASE

1991 ◽  
pp. 135-142
Author(s):  
Yoshihiro Miyake ◽  
Kiyoshi Fukui ◽  
Kyoko Momoi ◽  
Fusao Watanabe ◽  
Masazumi Tada ◽  
...  
Keyword(s):  
Amino Acid ◽  
Structure Function ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Biological Studies ◽  
Structure Function Relationship ◽  
Function Relationship ◽  
Relationship Of

scholarly journals A Histochemical Method for the Demonstration of Diphosphopyridine Nucleotide Diaphorase

1958 ◽  
Vol 4 (1) ◽  
pp. 29-38 ◽  
Author(s):  
Marvin M. Nachlas ◽  
Donald G. Walker ◽  
Arnold M. Seligman
Keyword(s):  
Gastric Mucosa ◽  
Rat Kidney ◽  
Succinic Dehydrogenase ◽  
Lactic Dehydrogenase ◽  
Histochemical Demonstration ◽  
Cytochemical Localization ◽  
Dehydrogenase System ◽  
Special Distribution ◽  
Almost All ◽  
Mucous Lining

The present investigation concerning the histochemical demonstration of DPN diaphorase follows the development of a new reagent, Nitro-BT, which has already been used successfully for the cytochemical localization of the succinic dehydrogenase system. The most consistently favorable results were obtained with the lactate-lactic dehydrogenase system buffered at pH 7.4. Using sections of rat kidney and stomach, it was found that the intensity of stain was optimal after 15 minutes incubation at 37°C., conducted aerobically. By appropriate variations in the substrate mixture it was possible to selectively demonstrate the histochemical distribution of certain DPN-linked dehydrogenases in addition to DPN diaphorase. This was made possible by the special distribution of some of these dehydrogenases which distinguished them from one another. Of the dehydrogenases studied the distribution pattern of ß-hydroxybutyric dehydrogenase was the most singular. In the gastric mucosa ß-hydroxybutyric dehydrogenase was restricted to the cells of the mucous lining epithelium and the gland necks; and in the kidney the enzyme was limited to the cells of the proximal convoluted tubule and thick limbs of Henle's loop. In contrast, lactic dehydrogenase like DPN diaphorase was demonstrable in almost all cytologic elements of both the stomach and the kidney.

scholarly journals Action of S-carbamoyl and S-thiocarbamoyl derivatives of L-cysteine on L-amino acid oxidase.

1984 ◽  
Vol 48 (12) ◽  
pp. 3157-3159 ◽  
Author(s):  
Tomio KIMURA ◽  
Nobuyoshi ESAKI ◽  
Hidehiko TANAKA ◽  
Kenji SODA
Keyword(s):  
Amino Acid ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Derivatives Of

Methylated derivatives of l-tyrosine in reaction catalyzed by l-amino acid oxidase: isotope and inhibitory effects

2020 ◽  
Vol 168 (5) ◽  
pp. 509-514
Author(s):  
Małgorzata Pająk
Keyword(s):  
Amino Acid ◽  
Bond Cleavage ◽  
Isotope Effects ◽  
Antibacterial Properties ◽  
Competitive Inhibitor ◽  
Inhibitory Effect ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Enzyme Active Site ◽  
Derivatives Of

Abstract l-Amino acid oxidase (LAAO) is widely distributed in nature and shows important biological activity. It induces cell apoptosis and has antibacterial properties. This study was designed to investigate the effect of methyl substituent on its activity as methylated derivatives of l-tyrosine, labelled with short-lived B+ emitters, have been used in oncological diagnostics. To study isotope effects in the oxidative deamination of O-methyl-l-tyrosine, the deuterated isotopomer, i.e. O-methyl-[2-2H]-l-tyrosine, was synthesized by isotope exchange, catalyzed enzymatically by tryptophanase. Isotope effects were determined using the spectrophotometric non-competitive method. The values of isotope effects indicate that the α-C–H bond cleavage occurs in the rate determining step of the investigated reaction and α-hydrogen plays a role in the substrate binding process at the enzyme active site. The inhibitory effect on LAAO activity was studied with α-methyl-l-tyrosine and N-methyl-l-tyrosine. The mode of inhibition was determined based on Lineweavear–Burk plots intersections. α-Methyl-l-tyrosine has been found a mixed type inhibitor of the investigated enzyme, whereas N-methyl-l-tyrosine is a non-competitive inhibitor of LAAO.

Sign in / Sign up

Export Citation Format

Share Document